Pharmacological characterisation of the dopamine-sensitive adenylate cyclase in cockroach brain: Evidence for a distinct dopamine receptor

Abstract

Dopamine increases cyclic AMP production in crude membrane preparations of cockroach brain with plateaus in cyclic AMP production occurring between 1-10 μM and at 10 mM. Maximal production of cyclic AMP is 2.25 fold greater than that of control values. Octopamine also increases cyclic AMP production with a Ka of 1.4 μM and maximal production 3.5 fold greater than that of control. 5-Hydroxytryptamine does not increase cyclic AMP production. The effects of octopamine and dopamine are fully additive. The vertebrate dopamine agonists ADTN and epinine stimulate the dopamine-sensitive adenylate cyclase (AC) with Ka values of 4.5 and 0.6 μM respectively and with maximal effectiveness 1.7 fold greater than that of control. The selective D2-dopamine agonist LY-171555 stimulates cyclic AMP production to a similar extent with a Ka of 50 μM. Other dopamine agonists (apomorphine, SKF-82526, SKF-38393) have no stimulatory effects. The octopamine-sensitive AC is inhibited by a variety of antagonists known to affect octopamine and dopamine receptors, with the following order of potency: mianserin > phentolamine > cyproheptadine > piflutixol > cis-flupentixol > SCH-23390 > (+)-butaclamol > SKF-83566 > SCH-23388 > sulpiride > spiperone > haloperidol. The dopamine-sensitive AC is inhibited by the same compounds with the following order of potency: piflutixol > cis-flupentixol > (+)-butaclamol > spiperone ≥ SCH-23390 > cyproheptadine > SKF-83566 > SCH 23388 > mianserin > Phentolamine > sulpiride > haloperidol. With the exception of mianserin, 3H-piflutixol is displaced from brain membranes by dopamine antagonists with an order of potency similar to that observed for the inhibition of dopamine-sensitive AC. The results indicate that the octopamine- and dopamine-sensitive AC in cockroach brain can be distinguished pharmacologically and the dopamine receptors coupled to AC have pharmacological characteristics distinct from vertebrate D1- and D2-dopamine receptors. © 1987.